Anti-inflammatory effects induced by near-infrared light irradiation via M2 macrophage polarization.

Abstract Near-infrared (NIR) can penetrate into the dermis. NIR is able to regulate cutaneous component cells and immune cells, and shows significant anti-inflammatory therapeutic effects. However, the mechanisms of these effects are largely unknown. The purpose of this study is to elucidate NIR-induced molecular mechanisms on macrophages, since macrophages play initial roles in directing immune responses by their M1/M2 polarizations. Proteomic analysis revealed that NIR radiation enhanced the expression of mitochondrial respiratory gene citrate synthase (CS). This increased CS expression was triggered by NIR-induced histone-3-lysine-4 hypermethylation on the CS gene promoter, but not by heat, which led to macrophage M2 polarization and finally resulted in TGF-β1 release from CD4+ cells. These cellular effects were validated in human primary macrophages and abdominal NIR-irradiated mouse experiments. In a PMA-induced inflammatory model on mouse ear, we confirmed that NIR irradiation induced significant anti-inflammatory effects via decreased M1 counts, reduced TNF-α, and increased CCL22/TGF-β1 levels.